Approaches to quantify the contribution of multiple anemia risk factors in children and women from cross-sectional national surveys

Abstract

Background: Attributable fractions (AF) of anemia are often used to understand the multifactorial etiologies of anemia, despite challenges interpreting them in cross-sectional studies. We aimed to compare different statistical approaches for estimating AF for anemia due to inflammation, malaria, and micronutrient deficiencies including iron, vitamin A, vitamin B12, and folate.

Methods: AF were calculated using nationally representative survey data among preschool children (10 countries, total N = 7,973) and nonpregnant women of reproductive age (11 countries, total N = 15,141) from the Biomarkers Reflecting Inflammation and Nutrition Determinants of Anemia (BRINDA) project. We used the following strategies to calculate AF: 1) Levin's formula with prevalence ratio (PR) in place of relative risk (RR), 2) Levin's formula with odds ratio (OR) in place of RR, and 3) average (sequential) AF considering all possible removal sequences of risk factors. PR was obtained by 1) modified Poisson regression with robust variance estimation, 2) Kleinman-Norton's approach, and 3) estimation from OR using Zhang-Yu's approach. Survey weighted country-specific analysis was performed with and without adjustment for age, sex, socioeconomic status, and other risk factors.

Results: About 20-70% of children and 20-50% of women suffered from anemia, depending on the survey. Using OR yielded the highest and potentially biased AF, in some cases double those using PR. Adjusted AF using different PR estimations (Poisson regression, Kleinman-Norton, Zhang-Yu) were nearly identical. Average AF estimates were similar to those using Levin's formula with PR. Estimated anemia AF for children and women were 2-36% and 3-46% for iron deficiency, <24% and <12% for inflammation, and 2-36% and 1-16% for malaria. Unadjusted AF substantially differed from adjusted AF in most countries.

Conclusion: AF of anemia can be estimated from survey data using Levin's formula or average AF. While different approaches exist to estimate adjusted PR, Poisson regression is likely the easiest to implement. AF are a useful metric to prioritize interventions to reduce anemia prevalence, and the similarity across methods provides researchers flexibility in selecting AF approaches.

Fig 1

Estimated attributable fractions of anemia associated with iron deficiency in (A) preschool children and (B) women of reproductive age. Anemia defined as hemoglobin adjusted for altitude <11.0 g/dL for children and hemoglobin adjusted for altitude and smoking <12.0 g/dL for women. Inflammation-adjusted (using BRINDA regression adjustment method) ferritin concentrations <12 μg/L and <15 μg/L were used to define iron deficiency (ID) in children and women, respectively. Average AF (attributable fractions) (1) considers all exposure variables including inflammation, malaria, blood disorder, and other micronutrient deficiencies depending on data availability. Average AF (2) considers all exposure variables as above and further adjusts for age, sex (for children), and SES. Covariates for adjusted OR and adjusted PR included all available exposure variables, age, sex (for children), and SES. Adjusted AF were not available in Cambodia due to low prevalence of iron deficiency.

Fig 2

Estimated attributable fractions of anemia associated with inflammation in (A) preschool children and (B) women of reproductive age. Anemia defined as hemoglobin adjusted for altitude <11.0 g/dL for children and hemoglobin adjusted for altitude and smoking <12.0 g/dL for women. Inflammation defined as either CRP >5 mg/L or AGP >1 g/dL. Average AF (attributable fractions) (1) considers all exposure variables including malaria, blood disorder, and micronutrient deficiencies depending on data availability. Average AF (2) considers all exposure variables and adjusts for age, sex (for children), and SES. Covariates for adjusted OR and adjusted PR included all available exposure variables, age, sex (for children), and SES.

Fig 3

Estimated attributable fractions of anemia associated with malaria in (A) preschool children and (B) women of reproductive age. Anemia defined as hemoglobin adjusted for altitude <11.0 g/dL for children and hemoglobin adjusted for altitude and smoking <12.0 g/dL for women. Average AF (attributable fractions) (1) considers all exposure variables including malaria, blood disorder, and micronutrient deficiencies depending on data availability. Average AF (2) considers all exposure variables and adjusts for age, sex (for children), and SES. Covariates for adjusted OR and adjusted PR included all available exposure variables, age, sex (for children), and SES.

Fig 4. Estimated attributable fractions of anemia associated with blood disorder in preschool children.

Anemia defined as hemoglobin adjusted for altitude <11.0 g/dL. Average AF (attributable fractions) (1) considers all exposure variables including malaria, blood disorder, and micronutrient deficiencies depending on data availability. Average AF (2) considers all exposure variables and adjusts for age, sex (for children), and SES. Covariates for adjusted OR and adjusted PR included all available exposure variables, age, sex (for children), and SES.